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Principal Investigator: JOHN Christopher KAPPES
Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM
Fiscal Year: 2024
Award: $185,625
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
There are approximately 1.3 million transgender adults in the US, and about 467,000 of these individuals (~36%)
are transgender men. Transgender men are individuals who were assigned female at birth but identify as male.
Trans men may transition physiologically from female to male by receiving masculinizing hormone therapy and/or
hysterectomy. Those in the trans male community participate in diverse sexual behaviors and lifestyles resulting
in unique risks to STIs, especially HIV-1. Currently, there is a significant knowledge gap of the impact of HIV-1
on trans men, including limited knowledge regarding the effects of testosterone therapy on HIV-1 susceptibility
and acquisition. Over 70% of trans men receive testosterone to promote masculine characteristics and reduce
secondary female sex characteristics. Trans men treated with testosterone report symptoms of vaginal dryness
and loss of elasticity, which increase mucosal tissue breaks, which contribute to increased risk of HIV-1
transmission in trans men. Trans men treated with testosterone for at least one year have significantly reduced
levels of Lactobacillus comprising the vaginal microbiome, which correlates with bacterial vaginosis, and thus
increased risk of HIV transmission. Like other androgens, testosterone is a steroid hormone that interacts with
many different cell types, broadly affecting both innate and adaptive immunity through its effect on toll-like
receptors, immune-response cells, and pro- and anti-inflammatory cytokines. Testosterone has broad-ranging
effects on adaptive and innate immune functions and acts in a dynamic and often antagonistic manner with other
androgens, particularly dehydroepiandrosterone (DHEA), to modulate the development and function of immune
response cells. The central HYPOTHESIS of this research proposal is that testosterone alters cellular and
immunologic responses in the cervical mucosa that affect susceptibility to HIV-1 infection. To interrogate this
hypothesis, we propose to characterize certain cellular and innate immunologic properties of cervical mucosal
tissue obtained from transgender men receiving gender-affirming masculinizing therapy, and undergoing
medically indicated hysterectomies, and to correlate these findings to tissue susceptibility to HIV-1 infection ex
vivo. We anticipate identifying specific alterations in the cervical mucosa that correlate with testosterone therapy
and altered susceptibility to HIV-1 infection. If successful, our findings will provide new underpinnings for future
hypothesis-driven research focused on HIV-1 prevention strategies for transgender men. The research
proposed in this R21 grant application is guided by the following SPECIFIC AIMS: 1. Determine the effects of
testosterone on the susceptibility of cervical explant tissue to HIV-1 infection and populations of T lymphocytes;
and 2. Determine the effects of testosterone treatment on cytokine and chemokine expression in cervical tissue.
Terms: <21+ years old><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adult><Adult Human><Affect><Androgenic Agents><Androgenic Compounds><Androgens><Androstenolone><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Applications Grants><Bacterial Vaginitis><Bacterial Vaginosis><Biological><Body Tissues><Cell Body><Cells><Cellular Immune Function><Cervical><Characteristics><Chemotactic Cytokines><Community Participation><Coupled><DHEA><Dehydroisoandrosterone><Development><Elasticity><Endocrine Gland Secretion><Endocrine Therapy><Female><Frequencies><Future><Grant Proposals><HIV><HIV infection in mucosa><HIV mucosal challenge><HIV-1><HIV-1 infection in mucosa><HIV-1 mucosal challenge><HIV-I><HIV1><Homologous Chemotactic Cytokines><Hormonal Therapy><Hormones><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Hysterectomy><Immune response><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Individual><Infection><Innate Immunity><Intercrines><Knowledge><LAV-HTLV-III><Lactobacillus><Libido><Life Style><Lifestyle><Lymphadenopathy-Associated Virus><Masculine><Medical><Modeling><Mucosa><Mucosal Tissue><Mucous Membrane><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Nonspecific Vaginitis><Operative Procedures><Operative Surgical Procedures><Physiologic><Physiological><Population><Prasterone><Predisposition><Preventative strategy><Prevention strategy><Preventive strategy><Property><Reporting><Research><Research Proposals><Risk><Risk Factors><SIS cytokines><Sex Behavior><Sex Characteristics><Sexual Activity><Sexual Behavior><Surgical><Surgical Interventions><Surgical Procedure><Susceptibility><Symptoms><T-Cells><T-Lymphocyte><TLR protein><Testosterone><Therapeutic Androgen><Therapeutic Dehydroepiandrosterone><Therapeutic Hormone><Therapeutic Steroid Hormone><Therapeutic Testosterone><Tissues><Toll-Like Receptor Family Gene><Toll-like receptors><Trans-Testosterone><Transmission><Vagina><Virus-HIV><adaptive immunity><adulthood><assigned female at birth><assigned female gender at birth><assigned female sex at birth><biologic><cell type><chemoattractant cytokine><chemokine><cis-female><cis-gender woman><cis-woman><cisgender woman><cytokine><dehydroepiandrosterone><developmental><dry vagina><gender affirmation><gender affirmation hormone therapy><gender affirmation hormone treatment><gender affirming><gender affirming hormone therapy><gender affirming hormone treatment><gender identity affirmation><gender identity affirming><hormone therapy><host response><immune function><immune system response><immunoresponse><innate immune function><male><mucosal HIV infection><mucosal HIV-1 infection><non-specific vaginitis><sex activity><sex drive><sexual activities><sexual drive><steroid hormone><surgery><thymus derived lymphocyte><trans*><trans-men><transgender><transgender men><transman><transmen><transmission process><vagina dryness><vaginal biome><vaginal dryness><vaginal lactobacilli><vaginal microbiome>